Fenoterol

Publisher Website
Google Scholar
Abstract
Synopsis: Fenoterol, the 4-hydroxyphenyl derivative of orciprenaline, is a resorcinol derivative with relatively high selectivity for β2-adrenoceptors. It is active in man after inhalation or oral administration and is indicated in the treatment of bronchospasm associated with asthma, bronchitis and other obstructive airway diseases. Clinical experience has shown that fenoterol is an. effective bronchodilator with negligible effects on the cardiovascular system following aerosol administration of usual therapeutic doses. In children, inhaled fenoterol is effective in preventing exercise-induced asthma and administration of the aerosol in young children has been successfully used to terminate acute asthma attacks. In trials in adults, inhaled fenoterol was superior to placebo. In other controlled studies, it showed a tendency to cause a slightly greater maximum improvement in airway function as assessed spirometrically, and to have a longer duration of action than inhaled orciprenaline, salbutamol or terbutaline, although in these trials statistically significant differences were often not found. The onset of maximum effect is less rapid than with isoprenaline but is longer lasting. About 60 % of the eventual maximum response to fenoterol is reached in the first few minutes after inhalation. Oral fenoterol is more effective than placebo, ephedrine or orciprenaline, and probably similar to salbutamol and terbutaline. Following usual aerosol doses, side-effects are minimal. Oral administration is associated with a higher incidence of side-effects than inhalation, including fine muscle tremor and tachycardia. Pharmacodynamic studies: Fenoterol is an effective bronchodilator in animals and man when given by inhalation or by the oral route, and is effective in preventing experimentallyproduced asthma in adults and children. Following the administration of spasmogenic agents, oral or inhaled fenoterol is superior to isoprenaline, orciprenaline, hexoprenaline and salbutamol in protecting against bronchospasm, and is longer-acting. Bronchodilator response after parenteral doses has not been well documented. Following usual aerosol doses, cardiac effects of fenoterol are minimal, but higher oral doses (10mg or more) and parenteral administration may significantly affect heart rate and blood pressure. Pharmacokinetic studies: Fenoterol is rapidly absorbed following oral ingestion or inhalation and is then conjugated primarily with sulphuric acid in man. Following oral doses of tritiated fenoterol, peak plasma levels of radioactivity were attained in about 2 hours and were mainly due to metabolites rather than fenoterol itself. Approximately 60 % of an oral dose is absorbed. Inhaled doses appear to undergo a 2-stage absorption process, the first independent of dose and the second similar to that following oral administration. Fenoterol is excreted rapidly via the kidneys and liver, mainly as sulphate conjugates. Therapeutic trials: Single-dose and a small number of longer-term studies have shown that inhaled fenoterol is superior to placebo and isoprenaline in clinical effectiveness. While comparative studies with inhaled orciprenaline, salbutamol and terbutaline often did not show a significant difference between the drugs tested, there was a tendency for fenoterol to produce a slightly greater maximum improvement in forced expiratory volume in 1 second and to have a longer duration of action. In oral dose studies, fenoterol was more effective than a placebo, ephedrine or orciprenaline. Most studies comparing oral fenoterol with oral salbutamol and terbutaline involved non-equivalent dose levels, but it is reasonable to expect the drugs to be similar in efficacy. Subcutaneous fenoterol produces rapid bronchodilatation but the duration of action is short, with rapid loss of effectiveness after 30 minutes. In asthmatic children, inhaled fenoterol aerosol is similar to salbutamol and orciprenaline in improving airway function, and doses of 200 to 400µg sprayed onto the buccal mucosa or under the tongue have been effective in treating acute attacks in young children. Side-effects: There have been few reports of side-effects following inhalation of usual therapeutic doses of fenoterol. Tachycardia, nervousness, palpitations and fine muscle tremor have been reported but do not occur frequently. Oral doses have resulted in a higher incidence, particularly of tachycardia and fine muscle tremor (usually the hands). Parenteral administration appears to increase heart rate significantly and may cause palpitations. Over-dosage may produce tachycardia, tremor, restlessness, palpitation and alterations in blood pressure. Dosage: Fenoterol may be given by metered aerosol containing 200µg per puff. Dosage for an acute attack in adults and children is 1 puff, repeated in 5 minutes if necessary. In preventive therapy regimens, the prophylactic dose in adults is up to 2 puffs, 2 or 3 times daily while in children 1 puff at night and 1 in the morning may be sufficient. The usual oral dosage employed has been 5 to 10mg 3 times daily.
Keywords